The incidence of tuberculosis and other Mycobacterial diseases in both the developing world and in HIV+ people in the developed world make this infection of primary importance in public health. Multi-drug resistant strains of M. tuberculosis and the incidence of disease in patients whose immune systems are compromised by HIV present complications that are a challenge to treat. Understanding human immune response to TB is critical to the development of novel and effective therapies. We would like to study the natural history of immune response to TB, concentrating on the reactivity of T lymphocytes and their subsets to tuberculoproteins during the early phase of infection. We will take blood samples soon as possible after diagnosis (week 0), subsequently at weeks 1, 2, 3, 4, 8, 16, 24 and 36, to study this response longitudinally. The number of reactive T cells will be derived from limiting dilution analysis and the expression of selected T cell surface antigens. Quantitative analysis of lymphokines such as IL-1, IL-2, IL-6, TNF- and IFN- will be carried out on samples of plasma and the supernatant fluids of antigen and lectin stimulated T cells and monocytes. In addition, cell mediated delayed type immunity will be studied longitudinally by serial PPD skin tests allowing analysis of the nature, persistence and functional properties of mononuclear cells infiltrate. At a later date, cells from pleural effusion and broncho-alveolar lavage will be obtained to compare their immune function at the site of infection with that in peripheral blood. These studies could provide direction in the manipulation of human immune response to better control tuberculosis infection.